Skip to main content

Genetic and Epigenetic Control of Early Lymphocyte Development

  • Chapter
  • First Online:
Transcriptional Control of Lineage Differentiation in Immune Cells

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 381))

Abstract

T, B, and NK lymphocytes are generated from pluripotent hematopoietic stem cells through a successive series of lineage restriction processes. Many regulatory components, such as transcription factors, cytokines/cytokine receptors, and signal transduction molecules orchestrate cell fate specification and determination. In particular, transcription factors play a key role in regulating lineage-associated gene programs. Recent findings suggest the involvement of epigenetic factors in the maintenance of cell fate. Here, we review the early developmental events during lymphocyte lineage determination, focusing on the transcriptional networks and epigenetic regulation. Finally, we also discuss the developmental relationship between acquired and innate lymphoid cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  • Adolfsson J, Borge OJ, Bryder D, Theilgaard-Monch K, Astrand-Grundstrom I, Sitnicka E, Sasaki Y, Jacobsen SE (2001) Upregulation of Flt3 expression within the bone marrow Lin(−)Sca1(+)c-kit(+) stem cell compartment is accompanied by loss of self-renewal capacity. Immunity 15:659–669

    CAS  PubMed  Google Scholar 

  • Adolfsson J, Mansson R, Buza-Vidas N, Hultquist A, Liuba K, Jensen CT, Bryder D, Yang L, Borge OJ, Thoren LA, Anderson K, Sitnicka E, Sasaki Y, Sigvardsson M, Jacobsen SE (2005) Identification of Flt3 + lympho-myeloid stem cells lacking erythro-megakaryocytic potential a revised road map for adult blood lineage commitment. Cell 121:295–306

    CAS  PubMed  Google Scholar 

  • Agata Y, Tamaki N, Sakamoto S, Ikawa T, Masuda K, Kawamoto H, Murre C (2007) Regulation of T cell receptor beta gene rearrangements and allelic exclusion by the helix-loop-helix protein, E47. Immunity 27:871–884

    CAS  PubMed  Google Scholar 

  • Allman D, Sambandam A, Kim S, Miller JP, Pagan A, Well D, Meraz A, Bhandoola A (2003) Thymopoiesis independent of common lymphoid progenitors. Nat Immunol 4:168–174

    CAS  PubMed  Google Scholar 

  • Aloia L, di Stefano B, di Croce L (2013) Polycomb complexes in stem cells and embryonic development. Development 140:2525–2534

    CAS  PubMed  Google Scholar 

  • Balciunaite G, Ceredig R, Rolink AG (2005) The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage, and natural killer cell but no B-lymphocyte potential. Blood 105:1930–1936

    CAS  PubMed  Google Scholar 

  • Bell JJ, Bhandoola A (2008) The earliest thymic progenitors for T cells possess myeloid lineage potential. Nature 452:764–767

    CAS  PubMed  Google Scholar 

  • Broske AM, Vockentanz L, Kharazi S, Huska MR, Mancini E, Scheller M, Kuhl C, Enns A, Prinz M, Jaenisch R, Nerlov C, Leutz A, Andrade-Navarro MA, Jacobsen SE, Rosenbauer F (2009) DNA methylation protects hematopoietic stem cell multipotency from myeloerythroid restriction. Nat Genet 41:1207–1215

    PubMed  Google Scholar 

  • Busslinger M (2004) Transcriptional control of early B cell development. Annu Rev Immunol 22:55–79

    CAS  PubMed  Google Scholar 

  • Cales C, Roman-Trufero M, Pavon L, Serrano I, Melgar T, Endoh M, Perez C, Koseki H, Vidal M (2008) Inactivation of the polycomb group protein Ring1B unveils an antiproliferative role in hematopoietic cell expansion and cooperation with tumorigenesis associated with Ink4a deletion. Mol Cell Biol 28:1018–1028

    CAS  PubMed Central  PubMed  Google Scholar 

  • Christensen JL, Weissman IL (2001) Flk-2 is a marker in hematopoietic stem cell differentiation: a simple method to isolate long-term stem cells. Proc Natl Acad Sci USA 98:14541–14546

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cobaleda C, Jochum W, Busslinger M (2007) Conversion of mature B cells into T cells by dedifferentiation to uncommitted progenitors. Nature 449:473–477

    CAS  PubMed  Google Scholar 

  • de Pooter RF, Kee BL (2010) E proteins and the regulation of early lymphocyte development. Immunol Rev 238:93–109

    PubMed Central  PubMed  Google Scholar 

  • Dekoter RP, Singh H (2000) Regulation of B lymphocyte and macrophage development by graded expression of PU.1. Science 288:1439–1441

    CAS  PubMed  Google Scholar 

  • Dias S, Mansson R, Gurbuxani S, Sigvardsson M, Kee BL (2008) E2A proteins promote development of lymphoid-primed multipotent progenitors. Immunity 29:217–227

    CAS  PubMed Central  PubMed  Google Scholar 

  • Durum SK (2003) Bcl11: sibling rivalry in lymphoid development. Nat Immunol 4:512–514

    CAS  PubMed  Google Scholar 

  • Furusawa J, Moro K, Motomura Y, Okamoto K, Zhu J, Takayanagi H, Kubo M, Koyasu S (2013) Critical role of p38 and GATA3 in natural helper cell function. J Immunol 191:1818–1826

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gascoyne DM, Long E, Veiga-Fernandes H, de Boer J, Williams O, Seddon B, Coles M, Kioussis D, Brady HJ (2009) The basic leucine zipper transcription factor E4BP4 is essential for natural killer cell development. Nat Immunol 10:1118–1124

    CAS  PubMed  Google Scholar 

  • Godfrey DI, Kennedy J, Suda T, Zlotnik A (1993) A developmental pathway involving four phenotypically and functionally distinct subsets of CD3-CD4-CD8—triple-negative adult mouse thymocytes defined by CD44 and CD25 expression. J Immunol 150:4244–4252

    CAS  PubMed  Google Scholar 

  • Halim TY, Maclaren A, Romanish MT, Gold MJ, McNagny KM, Takei F (2012) Retinoic-acid-receptor-related orphan nuclear receptor alpha is required for natural helper cell development and allergic inflammation. Immunity 37:463–474

    CAS  PubMed  Google Scholar 

  • Hardy RR, Carmack CE, Shinton SA, Kemp JD, Hayakawa K (1991) Resolution and characterization of pro-B and pre-pro-B cell stages in normal mouse bone marrow. J Exp Med 173:1213–1225

    CAS  PubMed  Google Scholar 

  • Hattori N, Kawamoto H, Fujimoto S, Kuno K, Katsura Y (1996) Involvement of transcription factors TCF-1 and GATA-3 in the initiation of the earliest step of T cell development in the thymus. J Exp Med 184:1137–1147

    CAS  PubMed  Google Scholar 

  • Hidalgo I, Herrera-Merchan A, Ligos JM, Carramolino L, Nunez J, Martinez F, Dominguez O, Torres M, Gonzalez S (2012) Ezh1 is required for hematopoietic stem cell maintenance and prevents senescence-like cell cycle arrest. Cell Stem Cell 11:649–662

    CAS  PubMed  Google Scholar 

  • Hosoya T, Kuroha T, Moriguchi T, Cummings D, Maillard I, Lim KC, Engel JD (2009) GATA-3 is required for early T lineage progenitor development. J Exp Med 206:2987–3000

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hoyler T, Klose CS, Souabni A, Turqueti-Neves A, Pfeifer D, Rawlins EL, Voehringer D, Busslinger M, Diefenbach A (2012) The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells. Immunity 37:634–648

    CAS  PubMed Central  PubMed  Google Scholar 

  • Igarashi H, Gregory SC, Yokota T, Sakaguchi N, Kincade PW (2002) Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrow. Immunity 17:117–130

    CAS  PubMed  Google Scholar 

  • Ikawa T, Fujimoto S, Kawamoto H, Katsura Y, Yokota Y (2001) Commitment to natural killer cells requires the helix-loop-helix inhibitor Id2. Proc Natl Acad Sci USA 98:5164–5169

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ikawa T, Hirose S, Masuda K, Kakugawa K, Satoh R, Shibano-Satoh A, Kominami R, Katsura Y, Kawamoto H (2010) An essential developmental checkpoint for production of the T cell lineage. Science 329:93–96

    CAS  PubMed  Google Scholar 

  • Ikawa T, Kawamoto H, Fujimoto S, Katsura Y (1999) Commitment of common T/natural killer (NK) progenitors to unipotent T and NK progenitors in the murine fetal thymus revealed by a single progenitor assay. J Exp Med 190:1617–1626

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ikawa T, Kawamoto H, Goldrath AW, Murre C (2006) E proteins and notch signaling cooperate to promote T cell lineage specification and commitment. J Exp Med 203:1329–1342

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ikawa T, Kawamoto H, Wright LY, Murre C (2004) Long-term cultured E2A-deficient hematopoietic progenitor cells are pluripotent. Immunity 20:349–360

    CAS  PubMed  Google Scholar 

  • Ikuta K, Weissman IL (1992) Evidence that hematopoietic stem cells express mouse c-kit but do not depend on steel factor for their generation. Proc Natl Acad Sci USA 89:1502–1506

    CAS  PubMed Central  PubMed  Google Scholar 

  • Inlay MA, Bhattacharya D, Sahoo D, Serwold T, Seita J, Karsunky H, Plevritis SK, Dill DL, Weissman IL (2009) Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development. Genes Dev 23:2376–2381

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kamminga LM, Bystrykh LV, de Boer A, Houwer S, Douma J, Weersing E, Dontje B, de Haan G (2006) The polycomb group gene Ezh2 prevents hematopoietic stem cell exhaustion. Blood 107:2170–2179

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kawamoto H, Ikawa T, Masuda K, Wada H, Katsura Y (2010) A map for lineage restriction of progenitors during hematopoiesis: the essence of the myeloid-based model. Immunol Rev 238:23–36

    CAS  PubMed  Google Scholar 

  • Kennedy MK, Glaccum M, Brown SN, Butz EA, Viney JL, Embers M, Matsuki N, Charrier K, Sedger L, Willis CR, Brasel K, Morrissey PJ, Stocking K, Schuh JC, Joyce S, Peschon JJ (2000) Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice. J Exp Med 191:771–780

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kikuchi K, Lai AY, Hsu CL, Kondo M (2005) IL-7 receptor signaling is necessary for stage transition in adult B cell development through up-regulation of EBF. J Exp Med 201:1197–1203

    CAS  PubMed Central  PubMed  Google Scholar 

  • Klauke K, Radulovic V, Broekhuis M, Weersing E, Zwart E, Olthof S, Ritsema M, Bruggeman S, Wu X, Helin K, Bystrykh L, de Haan G (2013) Polycomb Cbx family members mediate the balance between haematopoietic stem cell self-renewal and differentiation. Nat Cell Biol 15:353–362

    CAS  PubMed  Google Scholar 

  • Klose CS, Hoyler T, Kiss EA, Tanriver Y, Diefenbach A (2012) Transcriptional control of innate lymphocyte fate decisions. Curr Opin Immunol 24:290–296

    CAS  PubMed  Google Scholar 

  • Kondo M, Weissman IL, Akashi K (1997) Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91:661–672

    CAS  PubMed  Google Scholar 

  • Kueh HY, Champhekhar A, Nutt SL, Elowitz MB, Rothenberg EV (2013) Positive feedback between PU.1 and the cell cycle controls myeloid differentiation. Science 341:670–673

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lee PP, Fitzpatrick DR, Beard C, Jessup HK, Lehar S, Makar KW, Perez-Melgosa M, Sweetser MT, Schlissel MS, Nguyen S, Cherry SR, Tsai JH, Tucker SM, Weaver WM, Kelso A, Jaenisch R, Wilson CB (2001) A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity 15:763–774

    CAS  PubMed  Google Scholar 

  • Lee SU, Maeda M, Ishikawa Y, Li SM, Wilson A, Jubb AM, Sakurai N, Weng L, Fiorini E, Radtke F, Yan M, Macdonald HR, Chen CC, Maeda T (2013) LRF-mediated Dll4 repression in erythroblasts is necessary for hematopoietic stem cell maintenance. Blood 121:918–929

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li L, Leid M, Rothenberg EV (2010a) An early T cell lineage commitment checkpoint dependent on the transcription factor Bcl11b. Science 329:89–93

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li P, Burke S, Wang J, Chen X, Ortiz M, Lee SC, Lu D, Campos L, Goulding D, Ng BL, Dougan G, Huntly B, Gottgens B, Jenkins NA, Copeland NG, Colucci F, Liu P (2010b) Reprogramming of T cells to natural killer-like cells upon Bcl11b deletion. Science 329:85–89

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li YS, Wasserman R, Hayakawa K, Hardy RR (1996) Identification of the earliest B lineage stage in mouse bone marrow. Immunity 5:527–535

    CAS  PubMed  Google Scholar 

  • Liu B, Liu YF, Du YR, Mardaryev AN, Yang W, Chen H, Xu ZM, Xu CQ, Zhang XR, Botchkarev VA, Zhang Y, Xu GL (2013) Cbx4 regulates the proliferation of thymic epithelial cells and thymus function. Development 140:780–788

    CAS  PubMed Central  PubMed  Google Scholar 

  • Liu P, Keller JR, Ortiz M, Tessarollo L, Rachel RA, Nakamura T, Jenkins NA, Copeland NG (2003) Bcl11a is essential for normal lymphoid development. Nat Immunol 4:525–532

    CAS  PubMed  Google Scholar 

  • Lu M, Tayu R, Ikawa T, Masuda K, Matsumoto I, Mugishima H, Kawamoto H, Katsura Y (2005) The earliest thymic progenitors in adults are restricted to T, NK, and dendritic cell lineage and have a potential to form more diverse TCRbeta chains than fetal progenitors. J Immunol 175:5848–5856

    CAS  PubMed  Google Scholar 

  • Lunardi A, Guarnerio J, Wang G, Maeda T, Pandolfi PP (2013) Role of LRF/pokemon in lineage fate decisions. Blood 121:2845–2853

    CAS  PubMed Central  PubMed  Google Scholar 

  • Maeda T, Merghoub T, Hobbs RM, Dong L, Maeda M, Zakrzewski J, van den Brink MR, Zelent A, Shigematsu H, Akashi K, Teruya-Feldstein J, Cattoretti G, Pandolfi PP (2007) Regulation of B versus T lymphoid lineage fate decision by the proto-oncogene LRF. Science 316:860–866

    CAS  PubMed Central  PubMed  Google Scholar 

  • Makar KW, Perez-Melgosa M, Shnyreva M, Weaver WM, Fitzpatrick DR, Wilson CB (2003) Active recruitment of DNA methyltransferases regulates interleukin 4 in thymocytes and T cells. Nat Immunol 4:1183–1190

    CAS  PubMed  Google Scholar 

  • Mandel EM, Grosschedl R (2010) Transcription control of early B cell differentiation. Curr Opin Immunol 22:161–167

    CAS  PubMed  Google Scholar 

  • Mansson R, Zandi S, Welinder E, Tsapogas P, Sakaguchi N, Bryder D, Sigvardsson M (2010) Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity. Blood 115:2601–2609

    CAS  PubMed  Google Scholar 

  • Massari ME, Murre C (2000) Helix-loop-helix proteins: regulators of transcription in eucaryotic organisms. Mol Cell Biol 20:429–440

    CAS  PubMed Central  PubMed  Google Scholar 

  • Masuda K, Kakugawa K, Nakayama T, Minato N, Katsura Y, Kawamoto H (2007) T cell lineage determination precedes the initiation of TCR beta gene rearrangement. J Immunol 179:3699–3706

    CAS  PubMed  Google Scholar 

  • Matsuzaki Y, Gyotoku J, Ogawa M, Nishikawa S, Katsura Y, Gachelin G, Nakauchi H (1993) Characterization of c-kit positive intrathymic stem cells that are restricted to lymphoid differentiation. J Exp Med 178:1283–1292

    CAS  PubMed  Google Scholar 

  • Medina KL, Pongubala JM, Reddy KL, Lancki DW, Dekoter R, Kieslinger M, Grosschedl R, Singh H (2004) Assembling a gene regulatory network for specification of the B cell fate. Dev Cell 7:607–617

    CAS  PubMed  Google Scholar 

  • Miyazaki M, Miyazaki K, Itoi M, Katoh Y, Guo Y, Kanno R, Katoh-Fukui Y, Honda H, Amagai T, van Lohuizen M, Kawamoto H, Kanno M (2008) Thymocyte proliferation induced by pre-T cell receptor signaling is maintained through polycomb gene product Bmi-1-mediated Cdkn2a repression. Immunity 28:231–245

    CAS  PubMed  Google Scholar 

  • Mjosberg J, Bernink J, Golebski K, Karrich JJ, Peters CP, Blom B, te Velde AA, Fokkens WJ, van Drunen CM, Spits H (2012) The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells. Immunity 37:649–659

    PubMed  Google Scholar 

  • Mochizuki-Kashio M, Mishima Y, Miyagi S, Negishi M, Saraya A, Konuma T, Shinga J, Koseki H, Iwama A (2011) Dependency on the polycomb gene Ezh2 distinguishes fetal from adult hematopoietic stem cells. Blood 118:6553–6561

    CAS  PubMed  Google Scholar 

  • Moro K, Yamada T, Tanabe M, Takeuchi T, Ikawa T, Kawamoto H, Furusawa J, Ohtani M, Fujii H, Koyasu S (2010) Innate production of T(H)2 cytokines by adipose tissue-associated c-Kit(+)Sca-1(+) lymphoid cells. Nature 463:540–544

    CAS  PubMed  Google Scholar 

  • Nechanitzky R, Akbas D, Scherer S, Gyory I, Hoyler T, Ramamoorthy S, Diefenbach A, Grosschedl R (2013) Transcription factor EBF1 is essential for the maintenance of B cell identity and prevention of alternative fates in committed cells. Nat Immunol 14:867–875

    CAS  PubMed  Google Scholar 

  • Neill DR, Wong SH, Bellosi A, Flynn RJ, Daly M, Langford TK, Bucks C, Kane CM, Fallon PG, Pannell R, Jolin HE, McKenzie AN (2010) Nuocytes represent a new innate effector leukocyte that mediates type-2 immunity. Nature 464:1367–1370

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nutt SL, Heavey B, Rolink AG, Busslinger M (1999) Commitment to the B-lymphoid lineage depends on the transcription factor Pax5. Nature 401:556–562

    CAS  PubMed  Google Scholar 

  • Nutt SL, Kee BL (2007) The transcriptional regulation of B cell lineage commitment. Immunity 26:715–725

    CAS  PubMed  Google Scholar 

  • Oguro H, Yuan J, Ichikawa H, Ikawa T, Yamazaki S, Kawamoto H, Nakauchi H, Iwama A (2010) Poised lineage specification in multipotential hematopoietic stem and progenitor cells by the polycomb protein Bmi1. Cell Stem Cell 6:279–286

    CAS  PubMed  Google Scholar 

  • Okuyama K, Ikawa T, Gentner B, Hozumi K, Harnprasopwat R, Lu J, Yamashita R, Ha D, Toyoshima T, Chanda B, Kawamata T, Yokoyama K, Wang S, Ando K, Lodish HF, Tojo A, Kawamoto H, Kotani A (2013) MicroRNA-126-mediated control of cell fate in B-cell myeloid progenitors as a potential alternative to transcriptional factors. Proc Natl Acad Sci USA 110:13410–13415

    CAS  PubMed Central  PubMed  Google Scholar 

  • Osawa M, Hanada K, Hamada H, Nakauchi H (1996) Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell. Science 273:242–245

    CAS  PubMed  Google Scholar 

  • Pai SY, Truitt ML, Ting CN, Leiden JM, Glimcher LH, Ho IC (2003) Critical roles for transcription factor GATA-3 in thymocyte development. Immunity 19:863–875

    CAS  PubMed  Google Scholar 

  • Park IK, Qian D, Kiel M, Becker MW, Pihalja M, Weissman IL, Morrison SJ, Clarke MF (2003) Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature 423:302–305

    CAS  PubMed  Google Scholar 

  • Pongubala JM, Northrup DL, Lancki DW, Medina KL, Treiber T, Bertolino E, Thomas M, Grosschedl R, Allman D, Singh H (2008) Transcription factor EBF restricts alternative lineage options and promotes B cell fate commitment independently of Pax5. Nat Immunol 9:203–215

    CAS  PubMed  Google Scholar 

  • Porritt HE, Rumfelt LL, Tabrizifard S, Schmitt TM, Zuniga-Pflucker JC, Petrie HT (2004) Heterogeneity among DN1 prothymocytes reveals multiple progenitors with different capacities to generate T cell and non-T cell lineages. Immunity 20:735–745

    CAS  PubMed  Google Scholar 

  • Price AE, Liang HE, Sullivan BM, Reinhardt RL, Eisley CJ, Erle DJ, Locksley RM (2010) Systemically dispersed innate IL-13-expressing cells in type 2 immunity. Proc Natl Acad Sci USA 107:11489–11494

    CAS  PubMed Central  PubMed  Google Scholar 

  • Revilla IDR, Bilic I, Vilagos B, Tagoh H, Ebert A, Tamir IM, Smeenk L, Trupke J, Sommer A, Jaritz M, Busslinger M (2012) The B-cell identity factor Pax5 regulates distinct transcriptional programmes in early and late B lymphopoiesis. EMBO J 31:3130–3146

    Google Scholar 

  • Reynaud D, Demarco IA, Reddy KL, Schjerven H, Bertolino E, Chen Z, Smale ST, Winandy S, Singh H (2008) Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros. Nat Immunol 9:927–936

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rosmaraki EE, Douagi I, Roth C, Colucci F, Cumano A, di Santo JP (2001) Identification of committed NK cell progenitors in adult murine bone marrow. Eur J Immunol 31:1900–1909

    CAS  PubMed  Google Scholar 

  • Rothenberg EV (2012) Transcriptional drivers of the T-cell lineage program. Curr Opin Immunol 24:132–138

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rothenberg EV, Moore JE, Yui MA (2008) Launching the T-cell-lineage developmental programme. Nat Rev Immunol 8:9–21

    CAS  PubMed Central  PubMed  Google Scholar 

  • Satoh Y, Yokota T, Sudo T, Kondo M, Lai A, Kincade PW, Kouro T, Iida R, Kokame K, Miyata T, Habuchi Y, Matsui K, Tanaka H, Matsumura I, Oritani K, Kohwi-Shigematsu T, Kanakura Y (2013) The Satb1 protein directs hematopoietic stem cell differentiation toward lymphoid lineages. Immunity 38:1105–1115

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schebesta A, McManus S, Salvagiotto G, Delogu A, Busslinger GA, Busslinger M (2007) Transcription factor Pax5 activates the chromatin of key genes involved in B cell signaling, adhesion, migration, and immune function. Immunity 27:49–63

    CAS  PubMed  Google Scholar 

  • Schilham MW, Wilson A, Moerer P, Benaissa-Trouw BJ, Cumano A, Clevers HC (1998) Critical involvement of Tcf-1 in expansion of thymocytes. J Immunol 161:3984–3991

    CAS  PubMed  Google Scholar 

  • Schlenner SM, Madan V, Busch K, Tietz A, Laufle C, Costa C, Blum C, Fehling HJ, Rodewald HR (2010) Fate mapping reveals separate origins of T cells and myeloid lineages in the thymus. Immunity 32:426–436

    CAS  PubMed  Google Scholar 

  • Schwarz BA, Sambandam A, Maillard I, Harman BC, Love PE, Bhandoola A (2007) Selective thymus settling regulated by cytokine and chemokine receptors. J Immunol 178:2008–2017

    CAS  PubMed  Google Scholar 

  • Seet CS, Brumbaugh RL, Kee BL (2004) Early B cell factor promotes B lymphopoiesis with reduced interleukin 7 responsiveness in the absence of E2A. J Exp Med 199:1689–1700

    CAS  PubMed Central  PubMed  Google Scholar 

  • Semerad CL, Mercer EM, Inlay MA, Weissman IL, Murre C (2009) E2A proteins maintain the hematopoietic stem cell pool and promote the maturation of myelolymphoid and myeloerythroid progenitors. Proc Natl Acad Sci USA 106:1930–1935

    CAS  PubMed Central  PubMed  Google Scholar 

  • Spangrude GJ, Heimfeld S, Weissman IL (1988) Purification and characterization of mouse hematopoietic stem cells. Science 241:58–62

    CAS  PubMed  Google Scholar 

  • Spits H, Cupedo T (2012) Innate lymphoid cells: emerging insights in development, lineage relationships, and function. Annu Rev Immunol 30:647–675

    CAS  PubMed  Google Scholar 

  • Staal FJ, Luis TC, Tiemessen MM (2008) WNT signalling in the immune system: WNT is spreading its wings. Nat Rev Immunol 8:581–593

    CAS  PubMed  Google Scholar 

  • Staal FJ, Sen JM (2008) The canonical Wnt signaling pathway plays an important role in lymphopoiesis and hematopoiesis. Eur J Immunol 38:1788–1794

    CAS  PubMed Central  PubMed  Google Scholar 

  • Su IH, Basavaraj A, Krutchinsky AN, Hobert O, Ullrich A, Chait BT, Tarakhovsky A (2003) Ezh2 controls B cell development through histone H3 methylation and Igh rearrangement. Nat Immunol 4:124–131

    CAS  PubMed  Google Scholar 

  • Suzuki H, Duncan GS, Takimoto H, Mak TW (1997) Abnormal development of intestinal intraepithelial lymphocytes and peripheral natural killer cells in mice lacking the IL-2 receptor beta chain. J Exp Med 185:499–505

    CAS  PubMed Central  PubMed  Google Scholar 

  • Tadokoro Y, Ema H, Okano M, Li E, Nakauchi H (2007) De novo DNA methyltransferase is essential for self-renewal, but not for differentiation, in hematopoietic stem cells. J Exp Med 204:715–722

    CAS  PubMed Central  PubMed  Google Scholar 

  • Taghon T, Yui MA, Rothenberg EV (2007) Mast cell lineage diversion of T lineage precursors by the essential T cell transcription factor GATA-3. Nat Immunol 8:845–855

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ting CN, Olson MC, Barton KP, Leiden JM (1996) Transcription factor GATA-3 is required for development of the T-cell lineage. Nature 384:474–478

    CAS  PubMed  Google Scholar 

  • Trowbridge JJ, Snow JW, Kim J, Orkin SH (2009) DNA methyltransferase 1 is essential for and uniquely regulates hematopoietic stem and progenitor cells. Cell Stem Cell 5:442–449

    CAS  PubMed Central  PubMed  Google Scholar 

  • van de Pavert SA, Mebius RE (2010) New insights into the development of lymphoid tissues. Nat Rev Immunol 10:664–674

    PubMed  Google Scholar 

  • van den Boom V, Rozenveld-Geugien M, Bonardi F, Malanga D, van Gosliga D, Heijink AM, Viglietto G, Morrone G, Fusetti F, Vellenga E, Schuringa JJ (2013) Nonredundant and locus-specific gene repression functions of PRC1 paralog family members in human hematopoietic stem/progenitor cells. Blood 121:2452–2461

    PubMed  Google Scholar 

  • Verbeek S, Izon D, Hofhuis F, Robanus-Maandag E, te Riele H, van de Wetering M, Oosterwegel M, Wilson A, Macdonald HR, Clevers H (1995) An HMG-box-containing T-cell factor required for thymocyte differentiation. Nature 374:70–74

    CAS  PubMed  Google Scholar 

  • Wada H, Masuda K, Satoh R, Kakugawa K, Ikawa T, Katsura Y, Kawamoto H (2008) Adult T-cell progenitors retain myeloid potential. Nature 452:768–772

    CAS  PubMed  Google Scholar 

  • Walker JA, Barlow JL, McKenzie AN (2013) Innate lymphoid cells–how did we miss them? Nat Rev Immunol 13:75–87

    CAS  PubMed  Google Scholar 

  • Weber BN, Chi AW, Chavez A, Yashiro-Ohtani Y, Yang Q, Shestova O, Bhandoola A (2011) A critical role for TCF-1 in T-lineage specification and differentiation. Nature 476:63–68

    CAS  PubMed Central  PubMed  Google Scholar 

  • Welinder E, Mansson R, Mercer EM, Bryder D, Sigvardsson M, Murre C (2011) The transcription factors E2A and HEB act in concert to induce the expression of FOXO1 in the common lymphoid progenitor. Proc Natl Acad Sci USA 108:17402–17407

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wong SH, Walker JA, Jolin HE, Drynan LF, Hams E, Camelo A, Barlow JL, Neill DR, Panova V, Koch U, Radtke F, Hardman CS, Hwang YY, Fallon PG, McKenzie AN (2012) Transcription factor RORalpha is critical for nuocyte development. Nat Immunol 13:229–236

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu X, Satpathy AT, Kc W, Liu P, Murphy TL, Murphy KM (2013) Bcl11a controls Flt3 expression in early hematopoietic progenitors and is required for pDC development in vivo. PLoS One 8:e64800

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xu W, Carr T, Ramirez K, McGregor S, Sigvardsson M, Kee BL (2013) E2A transcription factors limit expression of Gata3 to facilitate T lymphocyte lineage commitment. Blood 121:1534–1542

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yamamoto R, Morita Y, Ooehara J, Hamanaka S, Onodera M, Rudolph KL, Ema H, Nakauchi H (2013) Clonal analysis unveils self-renewing lineage-restricted progenitors generated directly from hematopoietic stem cells. Cell 154:1112–1126

    CAS  PubMed  Google Scholar 

  • Yang L, Bryder D, Adolfsson J, Nygren J, Mansson R, Sigvardsson M, Jacobsen SE (2005) Identification of Lin(−)Sca1(+)kit(+)CD34(+)Flt3—short-term hematopoietic stem cells capable of rapidly reconstituting and rescuing myeloablated transplant recipients. Blood 105:2717–2723

    CAS  PubMed  Google Scholar 

  • Yang Q, Jeremiah Bell J, Bhandoola A (2010) T-cell lineage determination. Immunol Rev 238:12–22

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang Q, Monticelli LA, Saenz SA, Chi AW, Sonnenberg GF, Tang J, de Obaldia ME, Bailis W, Bryson JL, Toscano K, Huang J, Haczku A, Pear WS, Artis D, Bhandoola A (2013) T cell factor 1 is required for group 2 innate lymphoid cell generation. Immunity 38:694–704

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yang Q, Saenz SA, Zlotoff DA, Artis D, Bhandoola A (2011) Cutting edge: natural helper cells derive from lymphoid progenitors. J Immunol 187:5505–5509

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yashiro-Ohtani Y, He Y, Ohtani T, Jones ME, Shestova O, Xu L, Fang TC, Chiang MY, Intlekofer AM, Blacklow SC, Zhuang Y, Pear WS (2009) Pre-TCR signaling inactivates notch1 transcription by antagonizing E2A. Genes Dev 23:1665–1676

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yu S, Zhou X, Steinke FC, Liu C, Chen SC, Zagorodna O, Jing X, Yokota Y, Meyerholz DK, Mullighan CG, Knudson CM, Zhao DM, Xue HH (2012) The TCF-1 and LEF-1 transcription factors have cooperative and opposing roles in T cell development and malignancy. Immunity 37:813–826

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yuan J, Muljo SA (2013) Exploring the RNA world in hematopoietic cells through the lens of RNA-binding proteins. Immunol Rev 253:290–303

    PubMed Central  PubMed  Google Scholar 

  • Zandi S, Bryder D, Sigvardsson M (2010) Load and lock: the molecular mechanisms of B-lymphocyte commitment. Immunol Rev 238:47–62

    CAS  PubMed  Google Scholar 

  • Zheng W, Flavell RA (1997) The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89:587–596

    CAS  PubMed  Google Scholar 

  • Zhu J, Min B, Hu-Li J, Watson CJ, Grinberg A, Wang Q, Killeen N, Urban JF Jr, Guo L, PAUL WE (2004) Conditional deletion of Gata3 shows its essential function in T(H)1-T(H)2 responses. Nat Immunol 5:1157–1165

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Peter Burrows for critical reading of the manuscript. This work is supported in part by grants from the Japan Society for the Promotion of Science (24689042), the Japan Science and Technology Agency, RIKEN IMS-RCAI Young Chief Investigator program and Kanae Foundation for the Promotion of Medical Science.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tomokatsu Ikawa .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Ikawa, T. (2014). Genetic and Epigenetic Control of Early Lymphocyte Development. In: Ellmeier, W., Taniuchi, I. (eds) Transcriptional Control of Lineage Differentiation in Immune Cells. Current Topics in Microbiology and Immunology, vol 381. Springer, Cham. https://doi.org/10.1007/82_2014_370

Download citation

Publish with us

Policies and ethics